This invention relates generally to cyano-pyrrole, cyano-imidazole, cyano-pyrazole, and cyano-triazole compounds which are inhibitors of trypsin-like serine protease enzymes, especially factor Xa, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.
Inhibition of factor Xa may be more efficient than inactivation of thrombin in interrupting the blood coagulation system. Therefore, efficacious and specific inhibitors of factor Xa are needed as potentially valuable therapeutic agents for the treatment of thromboembolic disorders. It is thus desirable to discover new factor Xa inhibitors.
WO98/28269 describes factor Xa inhibitors of the formula: 
wherein ring M can be a variety of N-containing heterocycles including pyrrole, pyrazole, imidazole, and triazole and D is substituted meta or para to G on E. However, WO98/28269 does not disclose cyano-substituted compounds like those of the present invention.
WO98/57951 describes factor Xa inhibitors of the formula: 
wherein ring D is selected from xe2x80x94CH2Nxe2x95x90CHxe2x80x94, xe2x80x94CH2CH2Nxe2x95x90CHxe2x80x94, a 5-6 membered aromatic system containing from 0-2 heteroatoms selected from the group N, O, and S, ring E contains 0-2 N atom and M is a variety of rings including pyrrole, pyrazole, imidazole, and triazole. WO98/57951 does not, however, disclose cyano-substituted compounds like those of the present invention.
WO98/57937 describes factor Xa inhibitors of the formula: 
wherein ring D is phenyl or pyridyl and M is a variety of rings including pyrrole, pyrazole, imidazole, and triazole. However, WO98/57937 does not disclose cyano-substituted compounds like those of the present invention.
PCT/US98/26427 describes factor Xa inhibitors of the formula: 
wherein ring M is a variety of rings including pyrrole, pyrazole, imidazole, and triazole and D is substituted ortho to G on E. However, PCT/US98/26427 does not disclose cyano-substituted compounds like those of the present invention.
One object of the present invention is to provide novel cyano-pyrazole and cyano-triazole compounds which are useful as factor Xa inhibitors or pharmaceutically acceptable salts or prodrugs thereof.
It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
It is another object of the present invention to provide a method for treating thromboembolic disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
It is another object of the present invention to provide novel compounds for use in therapy.
It is another object of the present invention to provide the use of novel compounds for the manufacture of a medicament for the treatment of a thromboembolic disorder.
These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors"" discovery that compounds of formulae Ia, Ib, Ic, and Id: 
or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, D, E, R1a, and Z are defined below, are factor Xa inhibitors.